We recently observed that when cocaine is administered to rats prior to exercise it causes an exaggerated catecholamine response during exercise and a concomitant increase in glycogen degradation in muscle. These findings have practical relevance for exercise performance as well as health implications. Because this field of study (cocaine and exercise) has received little scientific attention, we wish to pursue our research goals further. this proposal has two general objectives. The first is to gain further insight into the combined physiological effects of cocaine and exercise. Using the cocaine-exercise-rat model (30 min of treadmill exercise after IV cocaine, 1-5 mg/kg) we plan to answer the following questions: 1) Are the effects of cocaine during exercise a function of the intensity of exercise? 2) What are the effects of chronic cocaine on adaptations to endurance training? 3) Does exercise training attenuate the effects of cocaine? and 4) Are the effects of cocaine similar to those of amphetamine? The second objective is mechanistic in nature and involves identifying how cocaine exerts its peripheral effects. This will be accomplished by exposing the animals to various perturbations such as adrenal enervation, adrenodemedullation, sympathectomy, and alpha and beta adrenoceptor antagonists and then exercising them under the influence of cocaine as described above. The normal rise in plasma catecholamine and the increase rate of glycogenolysis will serve as the criteria of measure in these studies. the results should clarify 1) whether the catecholamine response to cocaine is centrally mediated, peripherally mediated, or both, and 2) whether the rapid muscle glycogenolysis is linked to the cocaine- induced elevation in plasma catecholamine levels. Because knowledge concerning the peripheral effects of cocaine is severely lacking, the results from this proposal coupled with those from our first project will continue to fill the void. Eventually, we hope to extend our observations to the subcellular level using the tools of molecular biology, but we must cover this important ground first.